Preparation method of 3-selenium cyano indole compound

Abstract

The invention discloses a preparation method of a 3-selenium cyano indole compound. The preparation method comprises the following specific preparation process: carrying out illumination reaction on a compound as shown in a formula I, elemental selenium and trimethylsilyl cyanide in a reaction system containing an additive to prepare a target product compound as shown in a formula II, namely the 3-selenium cyano indole compound. According to the 3-selenium cyano indole compound and the preparation method thereof, in the organic solvent containing the additive, air is introduced to react under the blue LEDs irradiation condition to prepare a series of 3-selenium cyano indole compounds, the 3-selenium cyano indole compounds provided by the invention not only expand the variety of selenium cyano indole compounds, but also the preparation method provided by the invention is simple in operation process and high in yield, and the yield of the 3-selenium cyano indole compounds is greatly improved. And the preparation method is a simple preparation method of the 3-selenium cyano indole compound.

Description

Technical Field

[0001] The present invention belongs to the technical field of the synthesis of selenocyanato indole compounds, and particularly relates to a preparation method of 3-selenocyanato indole compounds. Background Art

[0002] 3-Substituted indoles have been widely used in the fields of pesticides, alkaloids, biopharmaceuticals, materials science, etc. As an important class of indole compounds containing selenium at the 3-position, especially in biology and medicine, the molecular structure of this kind of skeleton shows anti-tumor, antioxidant and antidepressant and other properties, which has attracted great attention of drug R & D workers.

[0003] In the past few decades, a variety of methods for preparing 3-selenocyanato indole compounds have been established. In 2002, the Nair group synthesized 3-selenocyanato indole with a yield of 72% using ammonium cerium nitrate as an oxidant and potassium selenocyanate as a selenocyanic acid source at 0 °C under an argon atmosphere; in 2004, the Kachanov group prepared 3-selenocyanato indole compounds using indole as a substrate and TSD in-situ generated from SeO 2 and malononitrile as a selenocyanic acid source. In 2016, a series of 3-selenocyanato indole compounds were prepared by catalyzing the reaction of indole derivatives with potassium selenocyanate using 10 mol% N-iodosuccinimide as a catalyst, tert-butyl hydroperoxide as an oxidant, and 3 equivalents of acetic acid as an additive. In 2018, the Jiang group completed the selenocyanation of indole using potassium selenocyanate as a selenocyanic acid source by electrocatalysis. In 2020, the Cao Tuanwu group catalyzed the reaction of indole derivatives with potassium selenocyanate using 25 mol% iodine as a catalyst to prepare a series of 3-selenocyanato indole compounds. In 2021, the Chen research group achieved the selenocyanation of indole using N-selenocyanatobis(phenylsulfonyl)imide as an electrophilic selenation reagent. In 2022, the Argüello group synthesized 3-selenocyanato indole compounds with methyl groups attached to different positions of the benzene ring using potassium persulfate as an oxidant and potassium selenocyanate as a selenocyanic acid source under the irradiation of a 400 nm ultraviolet lamp.

[0004] Despite the above progress in the synthesis of 3-selenocyanato indole compounds, the developed methods have many disadvantages and limitations, such as relatively harsh oxidation conditions, the use of excessive oxidants, the use of a large amount of solvents in electrocatalysis, etc. Therefore, it is still of great significance and necessity to develop a general and economical catalytic system. Summary of the Invention

[0005] The purpose of the present invention is to provide a preparation method of 3-selenocyanato indole compounds to solve or alleviate the technical problems existing in the above-mentioned prior art.

[0006] To achieve the above object, the present invention adopts the following technical solution: A preparation method of 3-selenocyanatoindole compounds, and the specific preparation process is as follows: The compound shown in formula I, selenium element and trimethylsilyl cyanide are subjected to a photo-reaction in a reaction system containing an additive to obtain the target product, the compound shown in formula II, namely 3-selenocyanatoindole compounds;

[0007] The structural formula of the compound shown in formula I is:

[0008]

[0009] Wherein, R 4 is hydrogen, halogen, nitro, -CO 2 R 5 、alkyl, substituted alkyl, alkoxy or substituted alkoxy; R 5 is hydrogen, alkyl, substituted alkyl or aryl; R 6 is hydrogen or alkyl;

[0010] The structural formula of the compound shown in formula II is:

[0011]

[0012] Wherein, R 1 is defined the same as R 4 , R 2 is defined the same as R 5 , R 3 is defined the same as R 6 ;

[0013] The additive is one or more of Cs 2 CO 3 、Et 3 N, DABCO, DMAP and DBU.

[0014] Furthermore, the structural formula of the compound shown in formula II is:

[0015] A preparation method of 3-selenocyanatoindole compounds, and the specific preparation steps are as follows: The compound shown in formula I, selenium element and trimethylsilyl cyanide are added to a reaction system containing an additive, air is introduced, and the reaction is carried out under the irradiation of blue LEDs. After the reaction is completed, it is concentrated under vacuum, and then purified by silica gel column chromatography with petroleum ether / ethyl acetate to obtain the target product, the compound shown in formula II, namely 3-selenocyanatoindole compounds.

[0016] Furthermore, the molar ratio of the compound shown in formula I, selenium element and trimethylsilyl cyanide is 1:1.5:2.

[0017] Further, the molar ratio of the additive to the compound represented by Formula I is 0.1 to 2:1.

[0018] Further, the reaction system containing the additive is a mixed system containing the additive and an organic solvent, wherein the organic solvent is a mixed solvent of THF and EtOH.

[0019] Further, the volume ratio of THF to EtOH in the organic solvent is 1:1.

[0020] The present invention has the following advantages and beneficial effects compared with the prior art:

[0021] The present invention uses the compound represented by Formula I and the alkenyl compound as raw materials, and reacts in an organic solvent containing an additive under the irradiation of blue LEDs by introducing air to obtain a series of 3-selenocyanatoindole compounds. The 3-selenocyanatoindole compounds provided by the present invention not only expand the types of selenocyanatoindole compounds, but also the preparation method provided by the present invention has a simple operation process and is a simple preparation method of 3-selenocyanatoindole compounds. Description of the Drawings

[0022] Figure 1 1H NMR spectrum of compound 2a prepared in Example 1;

[0023] Figure 2 13C NMR spectrum of compound 2a prepared in Example 1. Detailed Description of the Invention

[0024] The above content of the present invention will be further described in detail below through examples, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples. All technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0025] Specific examples of the 3-selenocyanatoindole compounds of the present invention are as follows:

[0026] Example 1

[0027] The structural formula of compound 2a is as follows:

[0028]

[0029] The specific synthesis process is as follows: In air, add 1 mL of THF, 1 mL of EtOH, compound 1a (0.3 mmol), selenium (0.45 mmol, 35.6 mg), TSMCN (0.6 mmol, 59.5 mg), and DBU (0.3 mmol, 45.7 mg) to a 10 mL glass reaction tube. React the mixture under air and irradiation with blue LEDs, stir the reaction for 24 h, then concentrate under vacuum. Purify the crude product by silica gel column chromatography with petroleum ether / ethyl acetate to obtain the yellow solid compound 2a (59.8 mg, yield 90%).

[0030] The synthetic route of compound 2a is as follows:

[0031]

[0032] Compound 2a was subjected to NMR analysis, and the results are as Figure 1 and Figure 2 shown. The test results of compound 2a are as follows: 1 H NMR (500 MHz, CDCl 3 ): δ 8.86 (s, 1H), 7.70 (t, J = 4.5 Hz, 1H), 7.39 - 7.32 (m, 2H), 7.28 - 7.22 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ): 136.1, 132.0, 128.8, 123.9, 121.9, 119.7, 112.0, 102.1, 89.5. HRMS (ESI) exact mass calculated for C 9 H 5 N 2 Se [M - H] + 220.9623, found 220.9614.

[0033] Example 2

[0034] The structural formula of compound 2c is as follows:

[0035]

[0036] In air, 1 mL of THF, 1 mL of EtOH, compound 1c (0.3 mmol), selenium (0.45 mmol, 35.6 mg), TSMCN (0.6 mmol, 59.5 mg), and DBU (0.3 mmol, 45.7 mg) were added to a 10 mL glass reaction tube. The mixture was reacted in air under blue LEDs irradiation, stirred for 24 h, then concentrated under vacuum. The crude product was purified by silica gel column chromatography with petroleum ether / ethyl acetate to obtain yellow solid compound 2c (78.9 mg, yield 89%).

[0037] Compound 2c was subjected to NMR analysis, and the test results of compound 2c are as follows: 1 HNMR(500MHz,DMSO):δ12.27(s,1H),7.88(d,J=8.0Hz,2H),7.67(d,J=7.5Hz,1H),7.60(t,J=7.5Hz,2H),7.56-7.45(m,2H),7.33-7.23(m,2H); 13 C NMR(125MHz,DMSO):142.8,136.1,131.0,130.5,129.2,129.0,128.7,123.1,121.1,119.2,112.2,104.7,88.2.

[0038] Example 3

[0039] The structural formula of compound 2m is as follows:

[0040]

[0041] The specific synthesis process was as follows: In air, 1 mL of THF, 1 mL of EtOH, compound 1m (0.3 mmol), selenium (0.45 mmol, 35.6 mg), TSMCN (0.6 mmol, 59.5 mg), and DBU (0.3 mmol, 45.7 mg) were added to a 10 mL glass reaction tube. The mixture was reacted in air under blue LEDs irradiation, stirred for 24 h, then concentrated under vacuum. The crude product was purified by silica gel column chromatography with petroleum ether / ethyl acetate to obtain gray solid compound 2l (27.7 mg, yield 40%).

[0042] Compound 2m was subjected to NMR analysis, and the test results of compound 2m are as follows: 1 H NMR(500MHz,CDCl 3 ):δ7.75(d,J=7.5Hz,1H),7.40-7.30(m,4H),3.82(s,3H); 1313C NMR (125 MHz, CDCl 3 ): 137.3, 136.1, 129.6, 123.4, 121.6, 119.9, 110.2, 101.9, 87.3, 33.5.

[0043] Example 4

[0044] The structural formula of compound 2o is as follows:

[0045]

[0046] The specific synthesis process is as follows: In air, add 1 mL of THF, 1 mL of EtOH, compound 1o (0.3 mmol), selenium (0.45 mmol, 35.6 mg), TSMCN (0.6 mmol, 59.5 mg), and DBU (0.3 mmol, 45.7 mg) to a 10 mL glass reaction tube. React the mixture in air under the irradiation of blue LEDs, stir the reaction for 24 h, then concentrate under vacuum. Purify the crude product by silica gel column chromatography with petroleum ether / ethyl acetate to obtain gray solid compound 2o (38.7 mg, yield 58%).

[0047] Compound 2o was subjected to NMR analysis, and the test results of compound 2o are as follows: 1 1H NMR (500 MHz, DMSO): δ 12.44 (s, 1H), 8.37 - 8.32 (m, 1H), 8.00 (t, J = 4.5 Hz, 2H), 7.29 - 7.24 (m, 1H); 13 13C NMR (125 MHz, DMSO): 148.3, 144.1, 133.8, 127.3, 121.1, 117.1, 104.5, 88.5.

[0048] Using compounds 1b, 1d - 1k, 1m, and 1n as raw materials, referring to the preparation method of Example 1, 3 - selenocyanatoindole compounds 2b, 2d - 2k, 2m, and 2n were respectively prepared. The structures, yields, and NMR data of the corresponding compounds are shown in Table 1.

[0049] Table 1 Chemical structures and yields of 3 - selenocyanatoindole compounds

[0050]

[0051]

[0052] The above embodiments have described the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification only illustrates the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A method for preparing 3-selenocyanoindole compounds, characterized in that The specific preparation process is: the compound represented by formula I, selenium and trimethylsilyl cyanide are subjected to light irradiation reaction in a reaction system containing additives to obtain the target product compound represented by formula II, i.e., 3-selenocyanoindole compound; The structural formula of the compound shown in Formula I is: Among them, R 4 For hydrogen, halogen, nitro, -CO2R 5 , alkyl, substituted alkyl, alkoxy or substituted alkoxy; R 5 is hydrogen, alkyl, substituted alkyl or aryl; R 6 is hydrogen or alkyl; The structural formula of the compound shown in formula II is: Among them, R 1 With R 4 Definition consistent, R 2 With R 5 Definition consistent, R 3 With R 6 Definitions are consistent; The additive is one or more of Cs2CO3, Et3N, DABCO, DMAP and DBU.

2. The method for preparing 3-selenocyanine indole compounds according to claim 1, characterized in that The structural formula of the compound shown in formula II is:

3. The method for preparing 3-selenocyanine indole compounds according to claim 1 or 2, characterized in that The specific preparation steps are: adding the compound represented by formula I, selenium and trimethylsilyl cyanide to a reaction system containing additives, introducing air to react under the condition of blue LEDs irradiation, concentrating under vacuum after the reaction is completed, and then purifying by silica gel column chromatography with petroleum ether / ethyl acetate to obtain the target product compound represented by formula II, i.e., 3-selenocyanoindole compound.

4. The method for preparing 3-selenocyanoindole compounds according to claim 3, characterized in that: The molar ratio of the compound represented by formula I, selenium and trimethylsilyl cyanide is 1:1.5:

2.

5. The method for preparing 3-selenocyanoindole compounds according to claim 3, characterized in that: The molar ratio of the additive to the compound represented by formula I is 0.1 to 2:

1.

6. The method for preparing 3-selenocyanoindole compounds according to claim 3, characterized in that: The reaction system containing the additive is a mixed system containing the additive and an organic solvent, wherein the organic solvent is a mixed solvent of THF and EtOH.

7. The method for preparing 3-selenocyanoindole compounds according to claim 6, characterized in that: The volume ratio of THF to EtOH in the organic solvent is 1:1.

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